{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T20:13:59Z","timestamp":1783455239181,"version":"3.55.0"},"posted":{"date-parts":[[2026,7,4]]},"group-title":"Genetic and Genomic Medicine","reference-count":52,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T00:00:00Z","timestamp":1783123200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,4]]},"abstract":"<jats:sec>\n                  <jats:title>INTRODUCTION<\/jats:title>\n                  <jats:p>Alzheimer\u2019s disease (AD) is the leading cause of dementia worldwide. The retina shares molecular pathways with the brain, yet no study has systematically linked retinal gene expression to AD risk.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>We performed transcriptome-wide association studies (TWAS) using two independent retinal eQTL panels (Strunz et al., n = 311; EyeGEx, n = 406) and a large meta-analyzed AD genome-wide association study (GWAS) (Bellenguez et al., 111,326 cases, 677,663 controls). Genes were further validated with GWAS in the independent Alzheimer\u2019s Disease Sequencing Project (ADSP) using a matched eQTL-panel strategy.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>\n                    We identified 62 AD-associated genes across the two eQTL panels using Bellenguez et al. as the discovery cohort. Of these, 31 were replicated in the ADSP cohort. The findings highlight shared complement-mediated immune dysregulation (\n                    <jats:italic>CD55<\/jats:italic>\n                    ,\n                    <jats:italic>CD46, TREM2<\/jats:italic>\n                    ) and provide functional transcriptomic evidence to prioritize novel causal drivers of AD pathogenesis, including\n                    <jats:italic>STYX<\/jats:italic>\n                    and the\n                    <jats:italic>LRRC37<\/jats:italic>\n                    gene family.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>DISCUSSION<\/jats:title>\n                  <jats:p>Retinal data capture core AD genetic architecture and reveal novel risk genes, highlighting the retina as a molecularly informative tissue for dementia research.<\/jats:p>\n                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